| First Author | Liu Z | Year | 2021 |
| Journal | Immunity | Volume | 54 |
| Issue | 2 | Pages | 247-258.e7 |
| PubMed ID | 33444549 | Mgi Jnum | J:305557 |
| Mgi Id | MGI:6706399 | Doi | 10.1016/j.immuni.2020.11.020 |
| Citation | Liu Z, et al. (2021) A class of viral inducer of degradation of the necroptosis adaptor RIPK3 regulates virus-induced inflammation. Immunity 54(2):247-258.e7 |
| abstractText | The vaccine strain against smallpox, vaccinia virus (VACV), is highly immunogenic yet causes relatively benign disease. These attributes are believed to be caused by gene loss in VACV. Using a targeted small interfering RNA (siRNA) screen, we identified a viral inhibitor found in cowpox virus (CPXV) and other orthopoxviruses that bound to the host SKP1-Cullin1-F-box (SCF) machinery and the essential necroptosis kinase receptor interacting protein kinase 3 (RIPK3). This "viral inducer of RIPK3 degradation" (vIRD) triggered ubiquitination and proteasome-mediated degradation of RIPK3 and inhibited necroptosis. In contrast to orthopoxviruses, the distantly related leporipoxvirus myxoma virus (MYXV), which infects RIPK3-deficient hosts, lacks a functional vIRD. Introduction of vIRD into VACV, which encodes a truncated and defective vIRD, enhanced viral replication in mice. Deletion of vIRD reduced CPXV-induced inflammation, viral replication, and mortality, which were reversed in RIPK3- and MLKL-deficient mice. Hence, vIRD-RIPK3 drives pathogen-host evolution and regulates virus-induced inflammation and pathogenesis. |
